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Abstract: SA-OR86

Molecular Pathways Associated with Early Vascular Calcification in Pediatric CKD

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology


  • Bernardor, Julie, CHU de Nice, Nice, France
  • Bartosova, Maria, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Zhang, Conghui, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Marinovic, Iva, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • Herzog, Rebecca, Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Vienna, Austria
  • Kratochwill, Klaus, Christian Doppler Laboratory for Molecular Stress Research in Peritoneal Dialysis, Department of Pediatrics and Adolescent Medicine, Vienna, Austria
  • Farlay, Delphine, INSERM UMR 1033, Lyon, Auvergne-Rhônes-Alpes, France
  • Dijkgraaf, Ingrid, Universiteit Maastricht, Maastricht, Limburg, Netherlands
  • Jaminon, Armand, Universiteit Maastricht, Maastricht, Limburg, Netherlands
  • Schurgers, Leon J., Universiteit Maastricht, Maastricht, Limburg, Netherlands
  • Schmitt, Claus Peter, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany

Children with advanced stages of chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD) and vascular calcification (VC) may already occur during childhood. This study comprehensively investigated the molecular pathways underlying early VC in children with CKD stage 5.


Arterioles from children with normal renal function and CKD5, (median age 8.9 and 8.8 years) were analyzed using digital quantitative histomorphometry, von Kossa staining and 18F-sodium autoradiography (18F-NaF) for calcium deposit quantification. Arteriolar transcriptome and proteome analyses were followed by gene set enrichment (GSEA) and Ingenuity pathway analysis. Based on literature mining, a VC pathway library was established consisting of 442 biological processes and molecular functions and associated genes were extracted from Gene Ontology database. The identified key molecular mechanisms were validated in independent pediatric CKD5 cohorts (n=32) and healthy controls (n=20) using quantitative immunostaining.


Von Kossa staining did not reveal calcium deposits, but 18F-NaF autoradiography demonstrated arteriolar microcalcifications in children with CKD5. Compared to children with normal renal function, the arteriolar lumen/vessel ratio was reduced (p=0.001), due to intima and media thickening (p<0.0001/0.02), together with CD68+ macrophage infiltration in the subendothelial space (p=0.001/0.02). Multi-omics VC pathway analysis identified 30 pathways primarily associated with actin cytoskeleton, Wnt signaling, extracellular matrix (ECM) organization, complement activation, apoptosis, and ossification regulation. In independent age-matched cohorts, two components of the Wnt pathway, DKK3 and Wnt2b, were decreased (p=0.0004/0.009). Fibronectin-1, a major regulator of ECM, was identified as a hub gene in VC and showed reduced abundance in children with CKD5 (p=0.001). Arteriolar osteoglycin, involved in ectopic bone formation, was increased in CKD5 (p<0.001).


Arteriolar microcalcifications are already present in young children with CKD5. We provide a comprehensive analysis of underlying molecular pathways and identified processes involved in vascular remodeling which open new avenues for potential therapeutic targets.